chr12-109103562-T-C

Variant names:

Variant summary

Our verdict is . The variant received 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_080911.3(UNG):c.752T>C(p.Phe251Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

UNG
NM_080911.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.86

Publications

6 publications found

Variant links:

Genes affected

UNG (HGNC:12572): (uracil DNA glycosylase) This gene encodes one of several uracil-DNA glycosylases. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. Alternative promoter usage and splicing of this gene leads to two different isoforms: the mitochondrial UNG1 and the nuclear UNG2. The UNG2 term was used as a previous symbol for the CCNO gene (GeneID 10309), which has been confused with this gene, in the literature and some databases. [provided by RefSeq, Nov 2010]

UNG Gene-Disease associations (from GenCC):

hyper-IgM syndrome type 5
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

UNG links:

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new If you want to explore the variant's impact on the transcript NM_080911.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

REVEL computational evidence supports a deleterious effect, 0.74

PP5

Variant 12-109103562-T-C is Pathogenic according to our data. Variant chr12-109103562-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 12292.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080911.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNG	NM_080911.3	MANE Select	c.752T>C	p.Phe251Ser	missense	Exon 6 of 7	NP_550433.1	E5KTA5
	UNG	NM_003362.4		c.725T>C	p.Phe242Ser	missense	Exon 5 of 6	NP_003353.1	P13051-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UNG	ENST00000242576.7	TSL:1 MANE Select	c.752T>C	p.Phe251Ser	missense	Exon 6 of 7	ENSP00000242576.3	P13051-1
UNG	ENST00000336865.6	TSL:1	c.725T>C	p.Phe242Ser	missense	Exon 5 of 6	ENSP00000337398.2	P13051-2
UNG	ENST00000446767.2	TSL:1	n.*201T>C		3_prime_UTR	Exon 4 of 5	ENSP00000400287.2	Q68DM5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hyper-IgM syndrome type 5 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.66

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

3.8

PhyloP100

5.9

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-7.8

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Varity_R

0.99

gMVP

0.94

Mutation Taster

=3/97

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over